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RecruitingInterventionalPhase 1/Phase 2

Phase I/II, Two-Part, Multicenter First-in-Human Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Subjects With Advanced Solid Malignant Tumors (IDeate-PanTumor01)

NCT ID: NCT04145622Sponsor: Daiichi SankyoLast updated: 2026-05-29

Summary

This is a single group study of participants with advanced solid tumors who have not been cured by other treatments. It is the first time the drug will be used in humans, and will be in two parts. The primary purpose of the parts are: * Dose Escalation Part: To evaluate the safety and tolerability and to determine the maximum tolerated dose and the recommended dose for expansion of ifinatamab deruxtecan (I-DXd). * Dose Expansion Part: To investigate the safety, tolerability and antitumor activity of I-DXd when administered as a single agent. This study is expected to last approximately 5 years from the time the first participant is enrolled to the time the last participant is off the study. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: * they withdraw * their disease gets worse * they experience unacceptable side effects.

Arms & interventions

  • DrugIfinatamab deruxtecan (I-DXd)

    A total anti-B7H3 antibody and MAAA-1181a

Outcome measures

Primary

  • Evaluate the incidence of dose-limiting toxicities (DLTs)

    Time frame: Day 1 to Day 21 in Cycle 1 in the dose escalation part

  • Evaluate the incidence of adverse events (AEs)

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Investigate the antitumor activity of ifinatamab deruxtecan (I-DXd)

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

Secondary

  • Characterize the PK parameter AUClast

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Characterize the PK parameter AUCtau

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Characterize the PK parameter Cmax

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Characterize the PK parameter Tmax

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Characterize the PK parameter Ctrough

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

  • Assess the incidence of anti-drug antibodies (ADAs)

    Time frame: Cycle 1 Day 1 through disease progression within 8 cycles (each cycle is 21 days)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by Investigator. Measurable lesions should not be from a previously irradiated site. If the lesion at a previously irradiated site is the only selectable target lesion, a radiological assessment showing significant progression of the irradiated lesion should be provided by the Investigator * Has adequate cardiac, hematopoietic, renal and hepatic functions * Has an adequate treatment washout period prior to start of study treatment * Has a pathologically documented advanced/unresectable or metastatic head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, squamous and adenocarcinoma non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bladder cancer, sarcoma, endometrial cancer, melanoma, adenocarcinoma CRPC (primary neuroendocrine or histologically confirmed neuroendocrine differentiated prostate cancer is not allowed), breast cancer that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. For Expansion Cohort 4 2L ESCC participants only: * Has disease progression a post platinum-based and an immune checkpoint inhibitor (ICI) treatment per global or local guidelines, with a maximum of one prior line of systemic therapy for unresectable advanced or metastatic ESCC. Exclusion Criteria: * Has prior treatment with B7-H3 targeted agent, including I-DXd. * Has had prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (e.g., trastuzumab deruxtecan) due to treatment-related toxicities. * Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial GI tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery. * Uncontrolled significant cardiovascular disease * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement, prior pneumonectomy, or requirement for supplemental oxygen * Has an uncontrolled infection requiring systemic therapy. * Has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the Investigator.

Study locations (15)

Cedars-Sinai Medical Center- Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048

Withdrawn

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

Recruiting
Site Coordinator · Contact

Florida Cancer Specialists

Orlando, Florida, 32804

Withdrawn

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting
Site Coordinator · Contact

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

Active Not Recruiting

Henry Ford Hospital

Detroit, Michigan, 48202

Active Not Recruiting

Washington University

St Louis, Missouri, 63110

Active Not Recruiting

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting
Site Coordinator · Contact

Columbia University Medical Center

New York, New York, 10032

Withdrawn

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

Active Not Recruiting

The Ohio State University

Columbus, Ohio, 43210

Withdrawn

Sidney Kimmel Cancer Center - Thomas Jefferson

Philadelphia, Pennsylvania, 19107

Withdrawn

SCRI Oncology Partners

Nashville, Tennessee, 37203

Active Not Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Active Not Recruiting

MDACC (MD Anderson Cancer Center)

Houston, Texas, 77030

Active Not Recruiting

References

  • Johnson ML, Patel MR, Falchook GS, Koyama T, Gutierrez M, Awad MM, Piha-Paul SA, Friedman CF, Satoh T, Okamoto N, Singh J, Yoshizuka N, Windish HP, Qian M, Tran BP, Doi T. Ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, in patients with advanced solid tumours (IDeate-PanTumor01): dose-escalation results from a phase 1/2 trial. Lancet Oncol. 2026 Apr;27(4):491-501. doi: 10.1016/S1470-2045(25)00733-8.(PubMed)